The present disclosure is generally related to cyclic carbonyl compounds for ring-opening polymerizations and methods of preparation thereof, and more specifically to cyclic carbonate compounds having a pendant pentafluorophenyl carbonate group. In addition, the disclosure also relates to the preparation of polymers having pendant pentafluorophenyl carbonate groups, which can be further reacted to form functionalized polymeric materials.
In general, the structural variety of cyclic carbonyl compounds for ring opening polymerization (ROP) is significantly less than the number of compounds available for controlled radical polymerization (CRP). However, as the effectiveness and operational simplicity of organocatalysts improves, a wider variety of ROP compounds is sought to generate polymer microstructures unique to ROP methods.
Initial efforts to employ substituted lactones as monomers for ROP were hampered by the sensitivity of the organocatalysts to steric bulk of the substituent groups, particularly those at the alpha-position. Since the alpha-position of cyclic esters is the only site capable of a general substitution reaction, this approach provided limited numbers of useful compounds. The finding that trimethylene carbonate (TMC) was efficiently polymerized by organocatalysts such as thiourea/1,8-diazabicyclo[5.4.0]undec-7-ene (TU/DBU) or 1,5,7-triaza-bicyclo[4.4.0]dec-5-ene (TBD) was encouraging, for two reasons: first, TMC-like compounds can be derived from readily available 1,3-diols, and second, the 1,3-diols can be chosen so as to only bear substituents at the 2-position, which becomes the 5-position in the cyclic carbonate, where the substituent does not interfere sterically with the ring-opening polymerization.
A number of cyclic carbonate compounds have been generated and polymerized in the past by more conventional anionic or organometallic ROP methods. Excessively bulky substituents (e.g., 2,2-diphenyl) in the 1,3-diol can make ring-opening of the corresponding cyclic carbonate thermodynamically unfavorable. Thus, efforts were focused on compounds derived from 2,2-bis(methylol)propionic acid (bisMPA), a common building block for biocompatible dendrimers. For example, cyclic carbonate compounds with a number of different functional groups attached to the carboxylate have been generated from bisMPA (Pratt et al. Chem Comm. 2008, 114-116), Scheme 1.
wherein X is O, NH, NR′, or S, and R′ and R generally represent groups comprising 1 to 30 carbons. The —COXR group can, for example, represent an ester, amide, or thioester derived from the bisMPA carboxylic acid.
The cyclic carbonate acid compound, MTCOH,
provides great versatility in preparing functionalized carbonate compounds for ROP, similar to (meth)acrylic acid for CRP. For example, the reaction of an alcohol or amine with (meth)acrylic acid (or (meth)acryloyl chloride) provides a (meth)acrylate or (meth)acrylamide compound for CRP. Likewise, the reaction of an arbitrary alcohol or amine with MTCOH (or its acid chloride) can generate a cyclic carbonate ester or cyclic carbonate amide compound for ROP.
However, there are only a few cyclic ester compounds bearing pendant carbonate or carbamate groups reported in the literature. For example, a cyclic carbonate bearing a chloroformate pendant group, MTCOCOCl, can be synthesized from tris(hydroxymethyl)ethane (TME) (Scheme 2).
Further substitution of the acyl chloride can afford functionalized carbonate compounds; however, the chloroformate intermediate suffers from the known limitations of acid chlorides (sensitivity to water, release of corrosive hydrogen chloride gas, difficulties in shipping and storing). In addition, this synthetic route is labor and resource intensive, uses significant amounts of solvent and reagents, and is not environmentally “green.”
Therefore, a need continues for improved methods of synthesis of cyclic ester compounds containing pendant carbonate or carbamate groups.
Biodegradable polymers are of intense for use in a variety of applications including drug delivery/target therapeutics, imaging agents, and tissue engineering. The two most common approaches to the synthesis of biodegradable polymers are the ring-opening polymerization (ROP) of cyclic esters (e.g., lactones) and cyclic carbonates to produce polyesters and polycarbonates, respectively, illustrated in Scheme 3.
wherein R1 and R2 generally represent hydrogen or a short chain monovalent hydrocarbon substituent, and n is 1 to 5. As a class of biodegradable polymers, polycarbonates have generally been found to exhibit significantly increased rates of biodegradation in the human body relative to polyesters.
MTCOH-based polymers have been widely reported with a variety of side chain groups. In these polymers, the side chain groups may be incorporated prior to polymerization via the synthesis of a functionalized monomer. Alternatively, cyclic carbonate monomers based on a protected variant of MTC-OH (most commonly the benzyl ester shown) can be polymerized and desired substituent groups later added to the polymer via post-polymerization modification (as shown in Scheme 4). This post-polymerization modification process typically encompasses removing the protecting group followed by coupling a new substituent group to the carboxylic acid group via the formation of an ester linkage, an amide linkage, or the like.

However, as a result of the limitations of the known art, few polymers bearing substituent groups attached by side-chain carbonate, carbamate, or other such linkages are known. A more versatile and straightforward approach to the preparation of ROP polymers bearing functionalized side chain groups is needed, in particular polycarbonates bearing reactive carbonate side chain groups. The reactive side chain groups should enable direct functionalization of the ROP polymer.